CHAPTER 19 CARBOXYLIC ACIDS C carboxylic acids, compounds of the type RCOH, constitute one of the most fre- quently encountered classes of organic compounds. Countless natural products are carboxylic acids or are derived from them. Some carboxylic acids, such as acetic acid, have been known for centuries. Others, such as the prostaglandins, which are pow- erful regulators of numerous biological processes, remained unknown until relatively recently. Still others, aspirin for example, are the products of chemical synthesis. The therapeutic effects of aspirin, welcomed long before the discovery of prostaglandins, are now understood to result from aspirins ability to inhibit the biosynthes (CH2)6CO,H CH2COH OCC Acetic acid PGE,(a prostaglandin; a small amount Aspirin of PGE, lowers blood pressure The chemistry of carboxylic acids is the central theme of this chapter. The impor tance of carboxylic acids is magnified when we realize that they are the parent com pounds of a large group of derivatives that includes acyl chlorides, acid anhydrides, esters, and amides. Those classes of compounds will be discussed in the chapter fol 736 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
CHAPTER 19 CARBOXYLIC ACIDS Carboxylic acids, compounds of the type , constitute one of the most frequently encountered classes of organic compounds. Countless natural products are carboxylic acids or are derived from them. Some carboxylic acids, such as acetic acid, have been known for centuries. Others, such as the prostaglandins, which are powerful regulators of numerous biological processes, remained unknown until relatively recently. Still others, aspirin for example, are the products of chemical synthesis. The therapeutic effects of aspirin, welcomed long before the discovery of prostaglandins, are now understood to result from aspirin’s ability to inhibit the biosynthesis of prostaglandins. The chemistry of carboxylic acids is the central theme of this chapter. The importance of carboxylic acids is magnified when we realize that they are the parent compounds of a large group of derivatives that includes acyl chlorides, acid anhydrides, esters, and amides. Those classes of compounds will be discussed in the chapter folCH3COH O Acetic acid (present in vinegar) HO OH O (CH2)6CO2H (CH2)4CH3 PGE1 (a prostaglandin; a small amount of PGE1 lowers blood pressure significantly) Aspirin COH O O OCCH3 RCOH O X 736 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.1 Carboxylic Acid Nomenclature lowing this one. Together, this chapter and the next tell the story of some of the most fundamental structural types and functional group transformations in organic and bio logical chemi 19.1 CARBOXYLIC ACID NOMENCLATURE owhere in organic chemistry are common names used more often than with the car- boxylic acids Many carboxylic acids are better known by common names than by their systematic names, and the framers of the IUPAC nomenclature rules have taken a lib- eral view toward accepting these common names as permissible alternatives to the sys- tematic ones. Table 19. 1 lists both the common and the systematic names of a number of important carboxylic acids. Systematic names for carboxylic acids are derived by counting the number of car bons in the longest continuous chain that includes the carboxyl group and replacing the -e ending of the corresponding alkane by -oic acid. The first three acids in the table, methanoic(I carbon), ethanoic (2 carbons), and octadecanoic acid(18 carbons), illus trate this point. When substituents are present, their locations are identified by number numbering of the carbon chain al ways begins at the carboxyl group. This is illustrated in entries 4 and 5 in the table TABLE 19.1 Systematic and Common Names of Some Carboxylic Acids Structural formula Systematic name Methanoic acid Formic acid CHCO,H Ethanoic acid CH3(CH,)16 CO2H Octadecanoic acid Stearic acid CH3CHCO2H Lactic acid HCO,H 2-Hydroxy-2-phenylethanoic acid Mandelic acid Propenoic acid Acrylic acid CH3(CH2)7 (Z)-9-Octadecenoic acid oleic acid -CO2H Benzenecarboxylic acid enzoic acid O-Hydroxybenzenecarboxylic acid alicylic acid HO2CCH2 CO2H Propanedioic acid HO2, CH2 CO2H Butanedioic acid Succinic acid CO2H 1, 2-Benzenedicarboxylic acid Phthalic acid CO2H Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
lowing this one. Together, this chapter and the next tell the story of some of the most fundamental structural types and functional group transformations in organic and biological chemistry. 19.1 CARBOXYLIC ACID NOMENCLATURE Nowhere in organic chemistry are common names used more often than with the carboxylic acids. Many carboxylic acids are better known by common names than by their systematic names, and the framers of the IUPAC nomenclature rules have taken a liberal view toward accepting these common names as permissible alternatives to the systematic ones. Table 19.1 lists both the common and the systematic names of a number of important carboxylic acids. Systematic names for carboxylic acids are derived by counting the number of carbons in the longest continuous chain that includes the carboxyl group and replacing the -e ending of the corresponding alkane by -oic acid. The first three acids in the table, methanoic (1 carbon), ethanoic (2 carbons), and octadecanoic acid (18 carbons), illustrate this point. When substituents are present, their locations are identified by number; numbering of the carbon chain always begins at the carboxyl group. This is illustrated in entries 4 and 5 in the table. 19.1 Carboxylic Acid Nomenclature 737 TABLE 19.1 Systematic and Common Names of Some Carboxylic Acids 1. 2. 3. 4. 5. 6. 7. 9. 10. 11. 12. 8. Methanoic acid Ethanoic acid Octadecanoic acid 2-Hydroxypropanoic acid 2-Hydroxy-2-phenylethanoic acid Propenoic acid (Z)-9-Octadecenoic acid o-Hydroxybenzenecarboxylic acid Propanedioic acid Butanedioic acid 1,2-Benzenedicarboxylic acid Systematic name Benzenecarboxylic acid Formic acid Acetic acid Stearic acid Lactic acid Mandelic acid Acrylic acid Oleic acid Benzoic acid Salicylic acid Malonic acid Succinic acid Phthalic acid Structural formula Common name HCO2H CH3CO2H CH3(CH2)16CO2H CH3CHCO2H W OH CH2œCHCO2H CH3(CH2)7 (CH2)7CO2H H H CœC ± ± ± ± HO2CCH2CO2H HO2CCH2CH2CO2H CHCO2H W OH CO2H CO2H OH CO2H CO2H Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER NINETEEN Carboxylic Acids Notice that compounds 4 and 5 are named as hydroxy derivatives of carboxylic acids, rather than as carboxyl derivatives of alcohols. We have seen earlier that hydroxyl groups take precedence over double bonds, and double bonds take precedence over halo- gens and alkyl groups, in naming compounds. Carboxylic acids outrank all the common groups we have encountered to this point Double bonds in the main chain are signaled by the ending -enoic acid, and their position is designated by a numerical prefix. Entries 6 and 7 are representative carboxylic acids that contain double bonds. Double-bond stereochemistry is specified by using either the cis-trans or the e-Z notation When a carboxyl group is attached to a ring, the parent ring is named(retaining the final -e) and the suffix - carboxylic acid is added, as shown in entries 8 and 9 Compounds with two carboxyl groups, as illustrated by entries 10 through 12,are distinguished by the suffix -dioic acid or-dicarboxylic acid as appropriate. The final -e in the base name of the alkane is retained PROBLEM 19.1 The list of carboxylic acids in Table 19. 1 is by no means exhaus- tive insofar as common names are concerned. many others are known by their common names, a few of which follow. Give a systematic IUPAC name for each (a) CH2-CCO,H (c) HO2 CCO2H (b)H3C CO,H CO2H (p-Toluic acid) SAMPLE SOLUTION (a)Methacrylic acid is an industrial chemical used in the preparation of transparent plastics such as lucite and Plexiglas. The carbon chain that includes both the carboxylic acid and the double bond is three carbon atoms in length. The compound is named as a derivative of propenoic acid. It is not nec essary to locate the position of the double bond by number, as in 2-propenoic acid, "because no other positions are structurally possible for it. The methyl group is at C-2, and so the correct systematic name for methacrylic acid is 2-methyl 19.2 STRUCTURE AND BONDING The structural features of the carboxyl group are most apparent in formic acid. Formic acid is planar, with one of its carbon-oxygen bonds shorter than the other, and with bond angles at carbon close to 1200 Bond distances Bond Angles H-C=0 134 H oxidization at carbon, and a o T carbon-oxygen double bond analogous to that of aldehydes and ketones Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Notice that compounds 4 and 5 are named as hydroxy derivatives of carboxylic acids, rather than as carboxyl derivatives of alcohols. We have seen earlier that hydroxyl groups take precedence over double bonds, and double bonds take precedence over halogens and alkyl groups, in naming compounds. Carboxylic acids outrank all the common groups we have encountered to this point. Double bonds in the main chain are signaled by the ending -enoic acid, and their position is designated by a numerical prefix. Entries 6 and 7 are representative carboxylic acids that contain double bonds. Double-bond stereochemistry is specified by using either the cis–trans or the E–Z notation. When a carboxyl group is attached to a ring, the parent ring is named (retaining the final -e) and the suffix -carboxylic acid is added, as shown in entries 8 and 9. Compounds with two carboxyl groups, as illustrated by entries 10 through 12, are distinguished by the suffix -dioic acid or -dicarboxylic acid as appropriate. The final -e in the base name of the alkane is retained. PROBLEM 19.1 The list of carboxylic acids in Table 19.1 is by no means exhaustive insofar as common names are concerned. Many others are known by their common names, a few of which follow. Give a systematic IUPAC name for each. (a) (c) (b) (d) SAMPLE SOLUTION (a) Methacrylic acid is an industrial chemical used in the preparation of transparent plastics such as Lucite and Plexiglas. The carbon chain that includes both the carboxylic acid and the double bond is three carbon atoms in length. The compound is named as a derivative of propenoic acid. It is not necessary to locate the position of the double bond by number, as in “2-propenoic acid,” because no other positions are structurally possible for it. The methyl group is at C-2, and so the correct systematic name for methacrylic acid is 2-methylpropenoic acid. 19.2 STRUCTURE AND BONDING The structural features of the carboxyl group are most apparent in formic acid. Formic acid is planar, with one of its carbon–oxygen bonds shorter than the other, and with bond angles at carbon close to 120°. This suggests sp2 hybridization at carbon, and a carbon–oxygen double bond analogous to that of aldehydes and ketones. Bond Distances CœO C±O 120 pm 134 pm Bond Angles H±CœO H±C±O O±CœO 124° 111° 125° C H O H O CH3 CO2H (p-Toluic acid) C H H CO2H H3C C (Crotonic acid) HO2CCO2H (Oxalic acid) CH2 CH3 CCO2H (Methacrylic acid) 738 CHAPTER NINETEEN Carboxylic Acids Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.3 Physical Properties Additionally, sp- hybridization of the hydroxyl oxygen allows one of its electron pairs to be delocalized by orbital overlap with the T system of the roup(Figure 19.1). In resonance terms, this electron delocalization is represented as H →>H—( OH OH Lone-pair donation from the hydroxyl oxygen makes the carbonyl group less elec trophilic than that of an aldehyde or ketone. The graphic that opened this chapter is an GURE 19.1 Carbon electrostatic potential map of formic acid that shows the most electron-rich site to be the and both oxygens g acid oxygen of the carbonyl group and the most electron-poor one to be, as expected, the OH The T component of the c=o group and the p or- Carboxylic acids are fairly acid, and benzoic acid have dipol system that includes carbo and the two oxygens 19.3 PHYSICAL PROPERTIES The melting points and boiling points of carboxylic acids are higher than those of hydro- carbons and oxygen-containing organic compounds of comparable size and shape and ndicate strong intermolecular attractive forces ng By Modeling and notice how much more intens carbon 2-Methyl-l-butene 2-Butanone 2-Butanol bp(I atm) 99°C A unique hydrogen-bonding arrangement, shown in Figure 19. 2, contributes to erties these attractive forces. The hydroxyl group of one carboxylic acid molecule acts as a proton donor toward the carbonyl oxygen of a second. In a reciprocal fashion, the n Appendix hydroxyl proton of the second carboxyl function interacts with the carbonyl oxygen of the first. The result is that the two carboxylic acid molecules are held together by two hydrogen bonds. So efficient is this hydrogen bonding that some carboxylic acids exist as hydrogen-bonded dimers even in the gas phase. In the pure liquid a mixture of hydrogen-bonded dimers and higher aggregates is present. In aqueous solution intermolecular association between carboxylic acid molecules is replaced by hydrogen bonding to water. The solubility properties of carboxylic acids are similar to those of alcohols. Carboxylic acids of four carbon atoms or fewer are mis cible with water in all proportions. FIGURE 19.2 Attrac positive(blue)and negative (red)electrostatic potentia ecular hydrogen bonding between two molecules of acetic acid Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Additionally, sp2 hybridization of the hydroxyl oxygen allows one of its unshared electron pairs to be delocalized by orbital overlap with the system of the carbonyl group (Figure 19.1). In resonance terms, this electron delocalization is represented as: Lone-pair donation from the hydroxyl oxygen makes the carbonyl group less electrophilic than that of an aldehyde or ketone. The graphic that opened this chapter is an electrostatic potential map of formic acid that shows the most electron-rich site to be the oxygen of the carbonyl group and the most electron-poor one to be, as expected, the OH proton. Carboxylic acids are fairly polar, and simple ones such as acetic acid, propanoic acid, and benzoic acid have dipole moments in the range 1.7–1.9 D. 19.3 PHYSICAL PROPERTIES The melting points and boiling points of carboxylic acids are higher than those of hydrocarbons and oxygen-containing organic compounds of comparable size and shape and indicate strong intermolecular attractive forces. A unique hydrogen-bonding arrangement, shown in Figure 19.2, contributes to these attractive forces. The hydroxyl group of one carboxylic acid molecule acts as a proton donor toward the carbonyl oxygen of a second. In a reciprocal fashion, the hydroxyl proton of the second carboxyl function interacts with the carbonyl oxygen of the first. The result is that the two carboxylic acid molecules are held together by two hydrogen bonds. So efficient is this hydrogen bonding that some carboxylic acids exist as hydrogen-bonded dimers even in the gas phase. In the pure liquid a mixture of hydrogen-bonded dimers and higher aggregates is present. In aqueous solution intermolecular association between carboxylic acid molecules is replaced by hydrogen bonding to water. The solubility properties of carboxylic acids are similar to those of alcohols. Carboxylic acids of four carbon atoms or fewer are miscible with water in all proportions. bp (1 atm): 2-Methyl-1-butene 31°C O 2-Butanone 80°C OH 2-Butanol 99°C O OH Propanoic acid 141°C H OH C O H C O OH H O C OH 19.3 Physical Properties 739 FIGURE 19.1 Carbon and both oxygens are sp2 - hybridized in formic acid. The component of the CœO group and the p orbital of the OH oxygen overlap to form an extended system that includes carbon and the two oxygens. A summary of physical properties of some representative carboxylic acids is presented in Appendix 1. Examine the electrostatic potential map of butanoic acid on Learning By Modeling and notice how much more intense the blue color (positive charge) is on the OH hydrogen than on the hydrogens bonded to carbon. FIGURE 19.2 Attractions between regions of positive (blue) and negative (red) electrostatic potential are responsible for intermolecular hydrogen bonding between two molecules of acetic acid. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
740 CHAPTER NINETEEN Carboxylic Acids 19. 4 ACIDITY OF CARBOXYLIC ACIDS Carboxylic acids are the most acidic class of compounds that contain only carbon, hydro- gen, and oxygen. With ionization constants Ka on the order of 10(pKa s 5), they ar much stronger acids than water and alcohols. The case should not be overstated, how- ever. Carboxylic acids are weak acids; a 0. 1 M solution of acetic acid in water, for exam To understand the greater acidity of carboxylic acids compared with water and alcohols, compare the structural changes that accompany the ionization of a representa- tive alcohol (ethanol) and a representative carboxylic acid(acetic acid). The equilibria that define K ar CH3CH2OH H+ CHCHO IHCH3CH,0 ICH3CH,OH Ethoxide ion lonization of acetic acid CH3COH H+ CHz CO k、田CH3CO2 [CH3CO2H) 18×10-5 From these Ka values, the calculated free energies of ionization (AGo) are 91 kJ/mol are calculated from equilib-(21.7 kcal/mol) for ethanol versus 27 kJ/mol (6.5 kcal/mol) for acetic acid. An energy rium constants according to diagram portraying these relationships is presented in Figure 19.3. Since it is equilibria, the relationship not rates, of ionization that are being compared, the diagram shows only the initial and △G°=-RTn final states. It is not necessary to be concerned about the energy of activation, since that affects only the rate of ionization, not the extent of ionization. The large difference in the free energies of ionization of ethanol and acetic acid reflects a greater stabilization of acetate ion relative to ethoxide ion lonization of ethanol yields an alkoxide ion in which the negative charge is localized on oxygen Solvation forces are the chief means by which ethoxide ion is stabilized. Acetate ion is also sta- bilized by solvation, but has two additional mechanisms for dispersing its negative charge that are not available to ethoxide ion: 1. The inductive effect of the carbonyl group. The carbonyl group of acetate ion is electron-withdrawing, and by attracting electrons away from the negatively charged oxygen, acetate anion is stabilized. This is an inductive effect, arising in the polar- ization of the electron distribution in the o bond between the carbonyl carbon and the negatively charged oxygen. Positively polarized CH2 group has carbon attracts elec- ons from negatively H on electron density CH3-CH, at negatively 2. The resonance effect of the carbonyl group. Electron delocalization, expressed by resonance between the following Lewis structures, causes the negative charge in acetate to be shared equally by both oxygens. Electron delocalization of this type is not available to ethoxide ion Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
19.4 ACIDITY OF CARBOXYLIC ACIDS Carboxylic acids are the most acidic class of compounds that contain only carbon, hydrogen, and oxygen. With ionization constants Ka on the order of 105 (pKa 5), they are much stronger acids than water and alcohols. The case should not be overstated, however. Carboxylic acids are weak acids; a 0.1 M solution of acetic acid in water, for example, is only 1.3% ionized. To understand the greater acidity of carboxylic acids compared with water and alcohols, compare the structural changes that accompany the ionization of a representative alcohol (ethanol) and a representative carboxylic acid (acetic acid). The equilibria that define Ka are Ionization of ethanol Ionization of acetic acid From these Ka values, the calculated free energies of ionization (G°) are 91 kJ/mol (21.7 kcal/mol) for ethanol versus 27 kJ/mol (6.5 kcal/mol) for acetic acid. An energy diagram portraying these relationships is presented in Figure 19.3. Since it is equilibria, not rates, of ionization that are being compared, the diagram shows only the initial and final states. It is not necessary to be concerned about the energy of activation, since that affects only the rate of ionization, not the extent of ionization. The large difference in the free energies of ionization of ethanol and acetic acid reflects a greater stabilization of acetate ion relative to ethoxide ion. Ionization of ethanol yields an alkoxide ion in which the negative charge is localized on oxygen. Solvation forces are the chief means by which ethoxide ion is stabilized. Acetate ion is also stabilized by solvation, but has two additional mechanisms for dispersing its negative charge that are not available to ethoxide ion: 1. The inductive effect of the carbonyl group. The carbonyl group of acetate ion is electron-withdrawing, and by attracting electrons away from the negatively charged oxygen, acetate anion is stabilized. This is an inductive effect, arising in the polarization of the electron distribution in the bond between the carbonyl carbon and the negatively charged oxygen. 2. The resonance effect of the carbonyl group. Electron delocalization, expressed by resonance between the following Lewis structures, causes the negative charge in acetate to be shared equally by both oxygens. Electron delocalization of this type is not available to ethoxide ion. CH3 C O Positively polarized O carbon attracts electrons from negatively charged oxygen. CH2 group has negligible effect on electron density at negatively charged oxygen. CH3 CH2 O Acetic acid CH3COH O Acetate ion CH3CO O H Ka [H][CH3CO2 ] [CH3CO2H] 1.8 105 Ethanol CH3CH2OH H Ethoxide ion CH3CH2O Ka [H][CH3CH2O] [CH3CH2OH] 1016 740 CHAPTER NINETEEN Carboxylic Acids Free energies of ionization are calculated from equilibrium constants according to the relationship G° RT In Ka Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website